Serotonin 3 Receptor Antagonist Market: Competitive Landscape, Pipeline, and Market Analysis 2022

Serotonin type 3 (5-HT3) receptors are pentameric ion channels belonging to the superfamily of Cys-loop receptors. Depending on their neural localization, 5-HT(3) receptors are known to be expressed in regions involved in the vomiting reflex, processing of pain, the reward system, cognition, and anxiety control, and in the periphery, they are known to be involved in emesis, pain disorders, drug addiction, psychiatric and GI disorders. Serotonin receptor (5-HT3) antagonists block serotonin both peripherally, on gastrointestinal vagal nerve terminals, and centrally in the chemoreceptor trigger zone, resulting in powerful antiemetic effects. Both orally and intravenously administered 5-HT3 blockers are indicated for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy including high-dose cisplatin therapy, and radiotherapy. Pfizer, Novartis, Sanofi, Roche, ADial Pharmaceuticals, and Das Therapeutics are currently providing serotonin 3 receptor antagonists for the treatment of cancer patients in the market.

Key Developments

• In Jan 2023, Samyang Group’s Emestop (Ramosetron Hydrochloride)’s comparison with Palonosetron in preventing postoperative nausea and vomiting in a meta-analysis resulted in no significant differences between the two drugs.
• In April 2023, Eisai and Merck’s E7386 in a phase 1b study in combination with Lenvatinib in patients with advanced hepatocellular carcinoma showed some promising activity.

Approved Drug Molecules for Serotonin 3 Receptor Antagonist

• SUSTOL (Granisetron)
• ADDYI (Flibanserin)
• Akynzeo (Netupitant and palonosetron)
• Auvelity (Dextromethorphan HBr -bupropion HCL)
• Emend (Aprepitant)
• Zofran (Ondansetron HCL)
• Invega (Paliperidone)
• Pepaxto (Melphalan flufenamide)
• Vraylar (cariprazine)
• Lybalvi (Olanzapine and Samidorphan)

Pipeline Molecules - Serotonin 3 receptor Antagonists

• Trenzapride (Azm 112) - Atlantic Healthcare
• Cvn-058 - Cerevance
• Granisetron Intranasal (Trg) - Shin Nippon Biomedical Labs
• Granisetron Transdermal (Syb-0701) - Synmosa Biopharma, SymBio Pharma
• Ondansetron Ultra-Low Dose (Ad04) - ADial Pharmaceuticals
• Ondansetron pyridostigmine (DAS-001) - DAS Therap
• Tedatioxetine (Lu Aa24530) - Takeda, Lundbeck
• R-azasetron besylate (SENS-401) - Sensorion
• TAK-058 - Takeda

Clinical Activity and Development of Serotonin 3 Receptor Antagonists

In the Serotonin 3 receptor antagonists, currently, there are 29 products, being operated by 32 pharmaceutical companies, including both approved drugs and drugs in clinical trials.

• In Jan 2021, Synmosa Biopharma, SymBio, and Abeillie Pharma’s Granisetron transdermal (SyB-0701) were compared with oral Granisetron in a meta-analysis, resulting in better achievement of oral Granisetron for completely controlling CINV in patients receiving chemotherapy.
• In Jan 2023, Samyang Groups’s Emestop’s (Ramosetron HCL) efficacy was compared with aqueous cinnamon extract, for partially attenuated bowel symptoms in the IBS model, which acted by directly inhibiting Tph1 expression and controlling 5-HT synthesis.
• In Mar 2023, Takeda and Lundbeck’s Trintellix (Vortioxetine) and tedatioxetin (Lu AA24530), and Lundbeck and Otsuka’s Rexulti (Brexipiprazole), in a study it was observed that Asian carriers of CYP2D6 decreased function alleles tended to exhibit higher CYP2D6 activity compared to Caucasians and Africans Americans, inter-ethnic differences within the CYP2D6 phenotype and genotype groups appeared to be driven by differences in CYP2D6 allele frequencies across ethnicities rather than inter-ethnic differences in enzyme activity for individuals carrying identical CYP2D6 genotypes.